This application addresses the thematic area, "Applying Genomics and Other High Throughput Technologies." The goal of this research project is to identify all genes that have fundamental roles in the neurobiological processes underlying learning, short-term memory, and retrieval. The project will capitalize on recent developments in "genomics" by using libraries of reagents (transgenic RNAi) that interfere with the expression of individual genes. The model system employed will be the fruit fly, Drosophila, because of the ease of working with this organism genetically, the availability of libraries of reagents that interfere with the expression of individual genes, and because Drosophila genes are known, in general, to have conserved functions in mammals. Flies carrying interfering RNAi transgenes for each individual Drosophila gene will be constructed and then trained and tested for odor learning. This will identify the set of genes required for acquisition of information, memory stability over a short period, and/or the retrieval of that stored information. The knowledge that emerges from this project will help reveal the molecular/cellular machinery for learning in Drosophila and will be tremendously useful for uncovering learning mechanisms in mammalian organisms including humans. Given that Drosophila "learning" genes are conserved both structurally and functionally, with some already implicated in human brain disorders, the knowledge gained from this project will also catalyze discoveries about the genetics of human neurological and psychiatric disorders and contribute to the development of drugs to treat impairments in cognition. PUBLIC HEALTH RELEVANCE: The majority of human neurological and psychiatric disorders involve impairment in learning and memory. This project will identify all genes in the genome of a model organism required for learning and memory. Since genes that are involved in learning are conserved between species, the knowledge from this project will contribute to understanding the genetics of human brain disorders and the development of drugs to treat impairments in cognition.